Epidemic keratoconjunctivitis (EKC) is caused by infection with the subgroup D adenovirus serotypes 8, 19, and 37, and is one of the most common human eye infections, causing significant morbidity and economic impact. EKC in highly contagious, manifests acutely with severe conjunctivitis and epithelial keratitis, and is associated with the delayed development of stromal (subepithelial) keratitis. Secondary dry eye, light sensitivity, and blurred vision can persist indefinitely. Surprisingly, although a group D adenovirus was identified as the cause of EKC over 40 years ago, the genetics of the adenovirus serotypes that cause EKC remain largely unknown. Our long term goal is to develop novel information-based approaches to prevention and therapy of the disorder. We hypothesize that genetic analyses of the adenoviruses associated with EKC will reveal specific viral pathogenesis traits that determine in part the manifestations of the disorder. This R03 proposal therefore specifically addresses a critical lack of information with regards to the genetics of these adenoviruses, and as such fills a stated purpose of the RO3 award, in that we propose to acquire "a body of data that has a potentially high impact on vision research". Recent similar efforts to elucidate the genetic code for other human pathogens have been received by the scientific community as seminal. The proposed collaboration between the principal investigator, a clinician-scientist with extensive expertise in virology and ocular infectious disorders, and the co-investigator, a microbial geneticist who has devoted his professional career to just the sort of study we propose, will likely result in highly significant and medically relevant interpretations of the resulting sequence data. Most importantly, successful completion of the proposed work will allow the study of the virology of ocular adenovirus infection in a fashion not currently possible. We propose a single specific aim: to determine and compare the genetic sequences of clinical adenovirus isolates from patients with EKC. To this end, adenoviruses will be collected from three major centers of clinical ophthalmology and sequenced. To other scientists, access to our data will be free and unencumbered via our web site. Genome-wide comparisons with other subgroup D adenoviruses for differences in nucleotide and predicted amino acid sequences will be performed using sequence alignment and analysis software, and are expected to reveal potential pathogenesis traits for future study.